The laboratory diagnosis of syphilis has relied, in large part, upon serologic methods for over 100 years (1). The causative organism, Treponema pallidum, is not amenable to in vitro culture, and antigen detection and nucleic acid amplification techniques have not become routinely used. While many of the serologic methods in use now have been in use for decades, their application, specifically the standard testing algorithm, is changing. In order to understand the interpretation of alternative testing algorithms, a thorough understanding of test characteristics is necessary. This chapter will review serologic tests for syphilis and their interpretation when they are applied to adults with and without HIV infection and to children.

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